208
A. BETZ
The system we are going to discuss now, the glycolytic oscillator, can
be considered as a model for biological timing systems. It is surely not the
basis of circadian rhythms. Whether or not it will be involved in control
of the beating heart muscle or contracting cilia is still an open question,
but it is one which is open to experiment, too.
Oscillatory fluctuations in glycolysis were observed independently by
CHANCE [3], DUYSENS [4], MATTHAEI [5] and others later. All of them saw
fluctuations in the level of reduced pyridinenucleotides during and following the transition to anaerobiosis in yeast cells. After the rediscovery of
oscillating NADH concentration in yeast by GHOSH [6] in Dr. CtIANCE'S
laboratory, the phenomenon was extensively studied there and at other
places. Since we learned to prepare a soluble extract from yeast cells [7],
it was obvious that control interactions between soluble enzymes acting
on soluble substrates are able to form an oscillator. In the meantime
FRENKEL [8], working with cell-free extracts of beef heart muscle, was able
to demonstrate oscillatory control in this system too. PRESSMAN [9] and
LARDY [10] observed potassium transport in rat liver mitochondria to
be a pulsatory process, like glycolysis in yeast. They subsequently established
a close connection between ion transport, shrinking and swelling and reduction of pyridinenucleotide in mitochondria. There are strong indications
from our own work [11] as well as from HOMMES [12] and MAITRA [13] that
glycolysis can continue to oscillate even under aerobic conditions. Oscillatory control in glycolysis is not merely the consequence of some disturbances in control.
The first question concerning this biochemical oscillator may be, how
far will it be able to fulfill the basic requirements for a timing system mentioned above.
First, there is constancy which means a self-sustaining, virtually undamped oscillator. Certainly, glycolytic oscillations in yeast cells are far
from being the undamped type. But with a cell-free extract PYE [14] was
able to demonstrate more than one hundred cycles of a nearly undamped
shape by adding trehalose, a substrate which is incorporated at a rather
slow rate. Recently BOITEUX [15] using a constant infusion technique
achieved genuinely undamped oscillations. This means that a biochemical
control system can become an essentially undamped oscillator, provided
that the influx of substrate is constant and of a suitable rate and further that
the end-products do not accumulate.
It is not strange that a metabolic oscillator can be triggered by substrate
addition. Glycolytic oscillations in cell-free extracts can be controlled not
only by substrates but even by other chemicals, which are involved only
as intermediates and whose concentrations are tightly balanced in glycolysis.
CHANCE [16] demonstrated in yeast extract that the addition of ADP at the
minimum of pyridine nucleotide reduction brought about an advance in
A. BETZ
The system we are going to discuss now, the glycolytic oscillator, can
be considered as a model for biological timing systems. It is surely not the
basis of circadian rhythms. Whether or not it will be involved in control
of the beating heart muscle or contracting cilia is still an open question,
but it is one which is open to experiment, too.
Oscillatory fluctuations in glycolysis were observed independently by
CHANCE [3], DUYSENS [4], MATTHAEI [5] and others later. All of them saw
fluctuations in the level of reduced pyridinenucleotides during and following the transition to anaerobiosis in yeast cells. After the rediscovery of
oscillating NADH concentration in yeast by GHOSH [6] in Dr. CtIANCE'S
laboratory, the phenomenon was extensively studied there and at other
places. Since we learned to prepare a soluble extract from yeast cells [7],
it was obvious that control interactions between soluble enzymes acting
on soluble substrates are able to form an oscillator. In the meantime
FRENKEL [8], working with cell-free extracts of beef heart muscle, was able
to demonstrate oscillatory control in this system too. PRESSMAN [9] and
LARDY [10] observed potassium transport in rat liver mitochondria to
be a pulsatory process, like glycolysis in yeast. They subsequently established
a close connection between ion transport, shrinking and swelling and reduction of pyridinenucleotide in mitochondria. There are strong indications
from our own work [11] as well as from HOMMES [12] and MAITRA [13] that
glycolysis can continue to oscillate even under aerobic conditions. Oscillatory control in glycolysis is not merely the consequence of some disturbances in control.
The first question concerning this biochemical oscillator may be, how
far will it be able to fulfill the basic requirements for a timing system mentioned above.
First, there is constancy which means a self-sustaining, virtually undamped oscillator. Certainly, glycolytic oscillations in yeast cells are far
from being the undamped type. But with a cell-free extract PYE [14] was
able to demonstrate more than one hundred cycles of a nearly undamped
shape by adding trehalose, a substrate which is incorporated at a rather
slow rate. Recently BOITEUX [15] using a constant infusion technique
achieved genuinely undamped oscillations. This means that a biochemical
control system can become an essentially undamped oscillator, provided
that the influx of substrate is constant and of a suitable rate and further that
the end-products do not accumulate.
It is not strange that a metabolic oscillator can be triggered by substrate
addition. Glycolytic oscillations in cell-free extracts can be controlled not
only by substrates but even by other chemicals, which are involved only
as intermediates and whose concentrations are tightly balanced in glycolysis.
CHANCE [16] demonstrated in yeast extract that the addition of ADP at the
minimum of pyridine nucleotide reduction brought about an advance in